Method of improving the immune response and compositions therefor

ABSTRACT

Method for enhancing the immune system of a patient by orally administering to the patient safflower seeds or an extract of safflower seeds in combination with a pharmaceutically acceptable vehicle.

This invention is a continuation-in-part of application Ser. No.09/080,129, filed on May 15, 1998, now U.S. Pat. No. 5,968,519 which inturn is a continuation-in-part of application Ser. No. 08/753,926, filedon Dec. 3, 1996, now U.S. Pat. No. 5,753,266.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a method of enhancing the immuneresponse of a mammal and compositions therefor.

2. Reported Developments

Rheumatoid arthritis (hereinafter sometimes referred to as RA) is acommon type of arthritis that causes inflammation in the lining of thejoints and sometimes other internal organs. RA tends to persist for manyyears, typically affects many different joints throughout the body, andultimately can cause damage to cartilage, bones, tendons and ligaments.RA is a chronic, inflammatory, connective-tissue disorder affecting morethan five million individuals in the U.S., and accounting forconsiderable disability in terms of missed work, lost wages, and reducedproductivity. The disease can occur at any age, but it most commonlybegins in the third to fifth decades of life.

The American College of Rheumotology has established criteria of thediagnosis of rheumatoid arthritis which include:

1. Morning stiffness lasting at least one hour;

2. Swelling of three or more joints;

3. Swelling of the wrist, metacarpophalangeal or proximal interphangealjoints;

4. Symmetric joint swelling;

5. Rheumatoid nodules;

6. Positive rheumatoid factor; and

7. Changes on hand radiographs typical of rheumatoid arthritis that mustinclude erosions or unequivocal bony decalcification.

The correct diagnosis of RA is essential for the clinician and involvescertain clinical, laboratory and radiological findings. The diagnosis isinfluenced by the age and sex of the patient, the pattern of jointinvolvement, the onset and course of the disease and extrarticularmanifestations.

In contrast to rheumatoid arthritis, osteoarthritis (hereinaftersometimes referred to as OA), the illness most often contemplated in thedifferential diagnosis, usually begins after the age of 50 and affectsmen and women equally. The joints involved in OA are different fromthose in RA and are not necessarily symmetrically affected. In OA, jointpathology is primarily mechanical, and synovial membrane inflammation isminimal.

As pertaining to the present invention certain other inflammatoryarthritis is differentiated from RA as listed in Table I.

TABLE I Differential Diagnosis of Rheumatoid Arthritis*

Seronegative spondyloarthropathy

(ankylosing spondylitis, reiters syndrome, psoriatic

arthritis, enteropathic arthritis)

Crystal-induced arthropathy

(gout, pseudogout)

Diffuse connective tissue disease

(systemic lupus erythematosus, polymyosiis,

fibromyalgia)

Infectious arthritis

Osteoarthritis

Polymyalgia rheumatica

Reactive arthritis

Hemoglobinopathies

Hemachromatosis

Lyme disease

Malignancy

Thyroid disease

Hemophilic arthropathy

Hypertrophic osteoarthritis

*Adapted from Textbook of Rheumatology.

Philadelphia, W.B. Saunders Co., 1989, pp 943-981.

With varying clinical significance, RA can at times affect other areasof the body. The most characteristic of these so-called extra-articularmanifestations are rheumatoid nodules. They can be found subcutaneouslyin up to 25% of rheumatoid patients, especially over extensor surfacesand in pressure areas. Common sites include the olecranon regions,fingers, Achilles tendons, the sacrum and the occiput. The presence ofsubcutaneous nodules is helpful diagnostically, because they areuncommon in the other forms of inflammatory arthritis. Nodules can alsooccur in visceral organs, including the lungs and the heart.

As discussed above, the primary cause of RA is unknown. It is thought tobe triggered by the presence of an as yet unidentified antigen(s) in animmunogenetically susceptible host, and the nature of the antigenresponsible for the arthritic reactions in RA has yet to be clearlyestablished.

Heretofore medical management of RA involved three general approaches.

The first is the use of aspirin and other nonsteroidal anti-inflammatoryanalgesics, and low-dose glucocorticoids to control the symptoms andsigns of the local inflammatory process. These agents are rapidlyeffective at mitigating symptoms and signs, but they appear to exertlittle effect on the progression of the disease.

A second group of drugs includes a variety of agents that have beenclassified as the disease-modifying drugs. These agents appear to havethe capacity to decrease elevated levels of acute phase reactants intreated patients, and therefore, are thought to modify the destructivecapacity of the disease.

The third class of agents includes the immunosuppressive and cytotoxicdrugs that have bee shown to ameliorate the disease process in somepatients. These last two classes of agents, however, often cause seriousside effects including the development of heart and liver diseases,increase in blood pressure, blindness and malignant neoplasms.

The prior art treatment of RA is based on the following two principles:first, RA is a systemic connective-tissue disorder that is notremediable solely through local measures. Second, RA is a progressivedisease that can potentially lead to severe cartilage and bonedestruction, organ damage, and decreased life expectancy. Currentregimens are predicated on controlling the immune system disturbance toreduce joint discomfort and destruction and this to maintain thepatient's activities of daily living.

Available drug preparations for the treatment of RA include thefollowing.

(1) NSAIDS Nonsteroidal Anti-Inflammatory Drugs

Pharmacologic treatment of RA has advanced steadily in the past severaldecades, but none of the agents used so far can cure RA. Aspirin remainsan important part of the treatment program for many people with RA. Tobe effective, it must be given in doses much higher than commonly usedas an over-the-counter remedy for minor aches and pains. Compared toother similar NSAIDS, aspirin is less expensive and its blood level canbe precisely measured. However, it can cause stomach problems in manypeople. Many physicians recommend the use of enteric (coated) forms ofaspirin.

NSAIDS are a large group of drugs that have mechanisms of action similarto aspirin. Like aspirin, these medications can relieve some of the painassociated with RA temporarily. The NSAIDS are the most frequentlyrecommended antirheumatic medications, and the first line of therapy inRA. As a result of the capacity of these agents to block the activity ofthe enzyme cyclooxygenase and therefore the production ofprostaglandins, prostacyclin and thromboxames, they have analgesic,anti-inflammatory and antipyretic properties. Table II lists the mostcommonly prescribed NSAIDS.

TABLE II Commonly Prescribed NSAIDS Grouped According To TheirElimination Half-Lives Short Acting Intermediate Acting Long Acting (6hours) (7 to 14 hours) (15 hours) Aspirin Diflunisal AzapropazoneDiclofenac Naproxen Nabumetone Etodolac Salsalate Oxaprozin FenoprofenSulindac Piroxicam Flufenamic acid Flurbiprofen Ibuprofen IndomethacinKetoprofen Meclofenamic acid Tolmetin

Table III lists the commonly prescribed NSAIDs by classification,half-life and dosage range.

TABLE III Commonly Prescribed NSAIDS Classification Half Life, hr DosageRange, mg/day Proprionic Acid Ibuprofen 2 1200-3200 Naproxen 13 250-1500 Fenoprofen 2 1200-3200 Ketoprofen 1.5 100-300 Oxaprozin 40 600-1800 Phenylacetic Acid Diclofenac 1.5 100-150 Indoleacetic AcidIndomethacin  3-11  50-200 Sulindac 16 300-400 Tolmetin 1-2  600-2000Fenamate Meclofenamate 2-3 200-400 Oxicam Piroxicam 30-86 20

These agents are all associated with a wide spectrum of toxic sideeffects. A common side effect of these drugs is bleeding from thestomach. Overall dose is limited by such gastrointestinal erosions, aswell as azotemia, platelet dysfunction, exacerbation of allergicrhinitis and asthma, liver function abnormalities, some renal andcardiovascular irritation, and CNS toxicity like tinnitus, althoughpatients occasionally differ unpredictably in their response to anindividual NSAID.

An individual's response to the various NSAIDS is quite variable.Gastrointestinal ulcerations develop in 0 to 30% of NSAID-treatedpatients. Duodenal lesions are less common than gastric ulcers. Thenephrotoxic effects of NSAIDS are well documented. Several mechanismsleading to renal prostaglandin synthesis may adversely affect renalblood flow and in certain situations, lead to acute insufficiency. Athigh risk are patients with minor or major pre-existing changes in renalfunction, such as those with changes related to aging, diabetesmellitus, hypertension, congestive heart failure, use of diuretics orlow salt diet, cirrhosis, and chronic renal failure of any other cause.

Once the diagnosis of rheumatoid arthritis has been firmly establishedas an insufficient response to local measures and NSAIDS determined, theaddition of DMARDs (disease modifying antirheumatic drugs) to theregimen is normally considered. These drugs include gold compounds,penicillamine, hydroxychloroquine, methotrexate and azathioprine.Estimated rates of efficacy and toxicity of these remittive agents isshown in Table IV.

TABLE IV Estimated Rates of Efficacy and Toxicity of Remittive AgentsEFFICACY EFFICACY TOXICITY High Intermediate High CyclophosphamideAzathioprine Parenteral gold Penicillamine Intermediate MethotrexateAuranofin Corticosteroids Sulfasalazine Low Hydroxychloroquine

The ability of these drugs to really modify the disease process iscontroversial. Unlike NSAIDS or Corticosteroids, their onset of actionis gradual over weeks to months. In addition, well-defined toxicity'scan occur with these drugs, and clinical laboratory monitoring must bejudicious. The response rate to the DMARDs is also variable, andpatients may gradually lose their positive benefits over time. Theyexert minimal direct nonspecific anti-inflammatory or analgesic effects,and therefore, NSAIDS must be continued during their administration,except in a few rare cases when true remissions are induced with them.Remittive agents have a wide spectrum of biological effects, but theirexact mechanism of action in RA is unknown. Each is associated withconsiderable toxicity and there is minimal evidence thatdisease-modifying drugs actually retard the development of bone erosionsor facilitate their healing. A brief description of each drug follows.

A. Hydroxychloroquine (Plaquenil)

Hydroxychloroquine is a drug originally developed for the treatment ofmalaria that has also been used for many years to treat RA and has beensomewhat effective among patients with mild to moderate RA. Drug-relatedadverse effects include gastrointestinal disturbances, skin rash,retinal pigmentary changes and visual impairment, and are morefrequently found among older patients. Regular eye examinations once ortwice a year because of potential damage to the retina is recommended,and Hydroxychloroquine must be discontinued at the first evidence ofvisual impairment.

B. Penicillamine (Depen, Cuprimine)

Penicillamine is equally effective in elderly and in younger RApatients. However, its rate of severe toxicity is high, and some adverseeffects such as serious skin rashes and taste abnormalities are morecommon in the older patient. Other adverse effects include nephropathy,bone marrow suppression, gastrointestinal disturbance, autoimmunesyndromes, liver toxicity and neuropathy secondary to pyridoxine(vitamin B6) deficiency. Penicillamine is also a slow-acting drug, thusbenefit may be achieved only after 3 to 6 months of use. Patients shouldbe monitored with blood counts and urine analyses weekly for the first 4weeks, then every 4 weeks, with tests of muscle and liver enzymesbiannually.

C. Parenteral Gold (Myochrysine, Solganal)

Parenteral gold (intramuscular sodium aurothiomalate or aurothioglucose)has been widely used for 60 years for the treatment of RA. However, goldmay lose its effectiveness over time in people who seem to benefit atfirst. furthermore, it often takes three to six months to determinewhether a person is getting benefits from gold salts and the drug isoften discontinued for lack of improvement after the 1000 mg dose isreached.

In some people gold treatment may slow down damage to cartilage andbone. This small group of people with RA experience long-lastingimprovement on gold injections, which are given weekly or six months orlonger, and can later be tapered to once every three weeks. However, theefficacy of parenteral gold is also hampered by its high rate oftoxicity, relative to other remittive agents. Adverse reactions mostfrequently encountered include skin rashes, oral ulcers, nephropathy andbone marrow suppression. Less common reactions are pneumonitis,enterocolitis and hepatitis. Patients should be monitored with bloodcounts and urine analyses before each injections, as well as physicalexamination to look for skin rash and oral ulcers.

D. Auzanofin (Ridaura)

Auranofin (oral gold) therapy appears to be less toxic but also lesseffective than parenteral gold. The spectrum of adverse effects issimilar to that of parenteral gold. However, the frequency ofgastrointestinal disturbances, especially diarrhea, is higher, whilefrequency of other toxicity's may be lower. Auranofin's beneficialeffects may be achieved only after 2 to 6 months of use. Patients shouldbe monitored with blood counts and urine analyses biweekly initially,then every month.

E. Sulfasalazine (Azulfadine)

Sulfasalazine has been reintroduced recently as a remittive agent in RA.It also appears to have a high toxicity ratio, with adverse effectsincluding skin rash, gastrointestinal disturbances, bone marrowsuppression, haemolysis, headaches, hepatotoxicity and pneumonitis. Itis contraindicated in patients with a known hypersensitivity to sulfurdrugs. There is a paucity of data regarding efficacy profiles. Moreelderly patients discontinue treatment mainly because ofgastrointestinal adverse effects. Patents should be monitored with bloodcounts, urine analyses and liver function tests biweekly initially, thenevery month. Sulfasalazine is not yet approved by the FDA for treatmentof RA.

F. Azathioprine (Imuran)

Azathioprine is an immunosuppressive drug that has gained widespread usein RA. Data are insufficient to asses its efficacy or toxicity profilesin the general population. It can help RA by suppressing overactivity ofthe immune system but also can increase susceptibility to certaininfections and lower blood counts. Common adverse effects include theaforementioned and increased risk of infections and the development ofmalignancies. It is recommended that elderly patients be monitored withblood counts and liver function tests biweekly initially, then everymonth.

G. Methotrexate (Rheumatrex)

Since the mid-1980's, methotrexate has become the most prescribedremittive agent for RA in many rheumatology centers. This is due to itshigher rate of efficacy and toxicity ratio relative to other remittiveagents, its rapid onset of action (mostly within 1 month) and convenientscheduling, with once-weekly dosage of pills or injections. It worksmore quickly than gold and maintains control of the disease in a largergroup population. Unlike gold, methotrexate cannot be taken lessfrequently after the first 6 to 12 months but instead, must be continuedevery week.

For the above reasons, methotrexate has proved comparatively effectivein controlling joint inflammation in many patients with RA and is oftenchosen first, especially for individuals with rapidly progressivedisease. However, long-term trials have indicated that methotrexate doesnot induce remission, but rather suppresses symptoms while it is beingadministered. The other agents are tried when less severe inflammationoccurs and if methotrexate has failed or has to be discontinued becauseof toxicity. However, age is positively related to methotrexatetoxicity. Adverse effects include oral ulcers, gastrointestinalsymptoms, alopecia, hepatotoxicity, pneumonitis and bone marrowsuppression. Transient elevations of liver enzymes occur frequently, buttheir long term significance is unclear, since they sometimes correlatewith histological abnormalities. Fibrosis has been reported in 30 to 52%of patients but there have been fewer reports of cirrhosis. Moreover,sequential liver biopsies in patients continuing methotrexate therapyshowed evidence of progression of abnormalities in hepatic architecture.Patients with pretreatment liver abnormalities, alcoholism or lungdiseases seem to be at increased risk of developing toxicity in theliver and lung, respectively. Patients should be monitored with bloodcounts and liver function tests weekly initially, then every month.Kidney functions tests and chest x-ray or pulmonary functions testsshould be performed once or twice per year.

H. Alkylating Agents

Alkylating agents cyclophosphamide (Cytoxan) and chlorambucil are verypowerful immunosuppressive drugs that are rarely prescribed for thetreatment of RA. Despite some proof of efficacy, they can be recommendedonly for patients with severe, relentless, active RA, not responding toother remittive agents or with serious complications outside the jointsuch as vasculitis (blood vessel inflammation). This is due to theirgreat risk of frequent and sometimes life-threatening adverse effects,which includes bone marrow suppression, increased susceptibility toinfection, and up to a 10-fold increase in the incidence of neoplasia.Other adverse effects are gastrointestinal intolerance, alopecia,pneumonitis and haemorrhagic cystitis. Patients should be monitored withweekly blood counts.

I. Corticosteroids

The role of Corticosteroids (cortisone, prednisone, and other similarmedications) in RA is still debated by physicians. In the short run, lowdose corticosteroids such as prednisone 5 to 10 mg or cortisone aresomewhat effective in some RA patients. However, prolongedadministration should be avoided because of long term adverse effects,even with low dosage regimens. These side effects are serious and withrespect to cortisone, can include easy bruising, osteoporosis (thinningof the bones), cataracts, weight gain, increased susceptibility toinfections, diabetes and high blood pressure. Dosage as low as 5 mg/dayof prednisone may suppress the hypothalamic-pituitary-adrenal axis.Other problems include sodium and fluid retention, hypertension,hyperglycaemis, osteoporosis, infections and skin changes.

For any patient taking a corticosteroid on a regular basis, carefulattention must be directed to proper calcium, vitamin and hormoneregulation. Corticosteroids sometimes are given an injection into one ormore joints or other areas of inflammation. Such injections may haveharmful side effects on the joints if given more than a few times a yearas shown in Table V.

TABLE V Side Effects of Corticosteroids*

Cataracts (posterior subcapsular)

Glaucoma

Hypertension

Congestive heart failure in predisposed patients

Peptic ulcer disease

Pancreatitis

Cushingoid Appearance (truncal obesity, moon faces)

Hyperglycemia

Secondary adrenal insufficiency

Electrolyte changes (sodium retention, hypokalemia)

Myopathy

Osteoporosis

Aseptic necrosis

Psychosis

Alterations in mood or personality

Pseudotumor cerebri

Thin fragile skin, ecchymoses

*Adapted from Textbook of Rheumatology, WB Saunders Co., 1989, p 852.

To date, long term management of RA has required a careful balance ofbenefit and risk; the estimated relative efficacy and toxicity ofremittive agents in patients. Usually therapy begins with the leasttoxic medications and NSAIDS are prescribed first. If further therapy isneeded, hydroxychloroquine, auranofin, or sulfasalazine is added inpatients with mild to moderate RA. Methotrexate or parenteral gold maybe given in patients with moderately severe disease, or with diseaseunresponsive to the former remittive agents. Penicillamine, azathioprineand particularly the alkylating agents are reserved for patients withrefractory disease. Low dosage prednisone is added for limited periodsof time as indicated above, while pulse-therapy with parenteralCorticosteroids can help in the induction of remission of RA. These canbe supplemented with intra-articular corticosteroid treatment.

We have now discovered compositions and methods for the treatment ofpatients suffering from minor to advanced arthritic conditions. Thecompositions of the present invention effectively replace alternative,state-of-the-art pharmaceutical remedies for persons suffering fromrheumatoid arthritis and rheumatoid-related inflammatory diseases.

We have also discovered that the compositions of the present inventioncan be effectively used in a regimen for delaying of menopause.

Menopause is defined in medial dictionaries as the cessation ofmenstruation in the human female. Menopause is better described as atransition period marking the closure of reproductive life, usuallyoccurring during mid-life. The average age at last menstrual period inthe U.S.A. is 51, though any time between age 40 and 59 falls within therealm of normal. As menopause approaches, the ovaries begin to fail andthere is a sudden dip in the female sex hormones, estrogen andprogesterone, which causes the cessation of menstruation. About 75 to80% of women have some symptoms related to the suddenness of estrogenwithdrawal.

Throughout most adult lives, the menstrual cycle operates in an expectedway, with hormones ebbing and flowing at levels just high enough to keepthe system in a comfortable balance. In early puberty, anovulatorycycles (months in which no egg has been produced by the ovary) aresignaled by heavier and longer bleeding than normal. The same happens inreverse as menopause approaches. In the months in which ovulation doesnot take place, periods tend to be heavier and longer. As premenopause(the time when periods are still regular) moves towards theperimenopause (the transition phase between regular periods and noperiods at all), monthly events become more unpredictable.

As used herein the definitions of certain terms are as follows.

The word “climacteric” describes the ongoing changes and symptoms ofmenopause, as it refers to a phase or transition period that my last for15-20 years, during which ovulation function and hormonal productsdecline. The climacteric can be divided into 3 stages: pre-, peri- andpostmenopause. (Menopause is the point in time signaling the end ofpremenopause and the beginning of postmenopause.) “Premenopause” refersto the years when the menstrual cycle is regular, or most of the femalereproductive life. It also refers to the early years of the climacteric,after the age of 40, when menstrual periods may become irregular andheavy. “Perimenopause” is the stage lasting several years on either sideof the last menstrual period. This time marks many physical changes.“Menopause” means the final menstrual period when the female has not hada menstrual period for 12 months. “Postmenopause” overlaps with the endof the perimenopausal stage and extends into the years following thelast menstrual period until the end of life.

During the reproductive years, two sources of estrogen production exist.The major source is the secretion of estradiol by granulosa cells ofovarian follicles. The second source involves extraglandulararomatization of plasma androstenedione. The endocrine change associatedwith the female climacteric are due mainly to the loss of estradiol.Cessation of estradiol secretion is attributed to loss of folliculargranulosa cells and to a decreased responsiveness of these cells tofollicle-stimulating hormones (FSH). These alterations cause themenstrual cycle initially to shorten and then gradually to lengthen asanovulaton occurs, and eventually to cease completely.

In postmenopausal women, estrogen production occurs almost exclusivelyby a mechanism known as “peripheral or extraglandular aromatization.”This utilizes circulating androstenedione, secreted primarily by theadrenals, and converts it to estrogen in tissue of fat, bone, muscle andbrain. Little, if any, estrogen is derived from ovarian or adrenalsecretion in menopausal women. In fact, plasma levels of estrogen do notchange if the ovaries are removed after menopause. The estrogenproduction in post-menopausal women is characterized by theextraglandular formation of a biologically weaker estrogen, namely,estrone, rather than by the ovarian secretion of the potent estrogen,namely estradiol.

Although the quantity of testosterone secreted by the menopausal ovarydoes not change from previous levels, testosterone becomes the principalsteroidal hormone secreted by the ovary. The growth of hair on the upperlip and chin of many elderly women may be due to diminished estrogenlevels and unopposed action of testosterone in these women. Pubicauxiliary and scalp hair are partially lost, residual hair becomescoarser, mainly due to degeneration of skin and loss of skin appendagesrather than to hormonal alterations.

Common symptoms associated with menopause are briefly describedhereunder.

There exists a wide range of symptoms that commonly affect women duringmenopause. Despite the documented occurrence of all of the ailments,most medical texts recognize three major physical ailments, which aremenstrual irregularity, hot flashes, and dry vagina (a.k.a.“genito-urinary distress”). Osteoporosis is occasionally listed as asymptom, but it is really a condition beginning long before menopause,but which may become critical during the menopausal years. Psychologicalailments (anxiety, depression and panic attacks) are viewed and handleddifferently depending on the source of the expert consulted.

Symptoms of menopause may be both long and short term. Short termsymptoms include hot flashes, night sweats, loss of libido. Long termsymptoms include the thinning and drying out of the vaginal and genitalskin and urinary troubles, which may all become permanent. Standardsings of menopause are:

1) Menstrual irregularity, or a fluctuation in the menstrual cycle.Periods may continue to arrive in a timely manner, but there are usuallyminor changes. For example, the period that lasted 3 or 4 days may lastfor 2 or 6; the flow might be much grater than typical or the color ofthe flow may change. All of this is normal, as is the increasingtendency to skip a period.

2) Hot flashes and night sweats, are another very common physicalsymptom. A hot flash is the sudden sensation of heat. When experiencedat night they are called night sweats. Cold chills are not uncommoneither. A hot flash is described as a sudden onset of warmth in the faceand neck that progresses to the chest, making the neck and face red. Itis estimated that 75 to 85% of American women experience hot flashes,marked by a rise in body temperature and a feeling of unbearable heat.The veins of the hands may tingle and swell. Perspiration may bead atthe hairline, between the breasts and down the back. Hot flashes canlast from one minute to an hour, but they usually last 2 to 3 minutesand are frequently associated with dizziness, nausea, headaches andpalpitations. They tend to appear during the time when menstrual periodsare erratic and to peak during the year of the last menstrual period.They seem to occur most often just before rising and just before bed.

The combination of a rise in skin temperature, peripheral vasodilation,a transient increase in heart rate and changes in skin impedance is alsoknown as vasomotor instability. 80% of women who experience hot flasheshave symptoms for more than 1 year, but less than 25% have symptoms formore than 5 years. It is said than not all post menopausal womenexperience vasomotor symptoms, perhaps because of alterations inmetabolism of catecholamine or catecholestrogen within the brain orbecause of extraglandular formation of estrone was sufficient in thesewomen to suppress the symptoms. Thus, it appears that hot flashes aretriggered by “estrogen withdrawal” rather than by a lack of estrogen.The exact mechanism(s) responsible for the vasomotor flush is unknown,although the hypothalamus is the likely site or origin of vasomotorflush.

3) Dry vagina and urinary distress. With menopause's onset , the tissueof the urethra and vagina tend to thin out and become more fragile. Thevagina may also become shorter and both urethra and vagina become morevulnerable to inflammation and infection. This atrophy of the epitheliumultimately leads to symptoms of irritation, burning, pruritis andvaginal bleeding at times. The loss of the vaginal epithelium correlateswith the extent of estrogen deprivation and tends to worsen with time.This condition is likely to occur a few years after menopause and maymean that a women's own lubrication is inadequate for pleasurable penilepenetration. The reduction of lubrication during intercourse is duemainly to a decrease in vaginal fluids, blood flow and glycogenproduction.

More specifically, during reproductive years the vaginal pH is between4.0 and 5.5 due to the production of glycogen-rich superficial cells. Asovarian function begins to wane, this maturational process is lost andthe vaginal pH increases to a range between 6.0 and 8.0. These changeslead to a higher incidence of vaginitis.

Even when vaginal or urinary problems are relatively minor, many womancomplain of frequent urination and a tendency to leak when coughing,sneezing or during orgasm. This is known as stress incontinence. Urgeincontinence is diagnosed when urine is dribbled on the way to thetoilet. Both conditions are treatable.

4) Osteoporosis, or “porous bone”, is a condition that results fromexcess loss of bone tissue. The onset is usually painless, with noadvance warning, except for occasional lower back pain as crushfractures happen. Because the pain eases after a few days, few womensuspect that a vertebra may have collapsed. The first awareness ofosteoporosis for most women is a fracture of some sort.

Normally the amount of new bone formed is equal to or greater than thatresorbed. In osteoporosis, bone resorption is greater than boneformation. Maximum bone density is reached between the ages of 25 and 36years. By the age of 45 to 50, the rate of bone resorption is greater inwomen than in men and more prevalent in Caucasians than in blacks. Afterour mid-30's, we begin to lose bone slowly at first and then morequickly in our late 40's and early 50's. Once menopause is past, boneloss slows down again.

Although we recognize an association between estrogen deprivation andprogressive loss of bone mass, the role of estrogen in the pathogenesisof post menopausal osteoporosis is still not entirely clear. The balancebetween the rate of bone formation and resorption is complex andinvolves a sensitive relationship between dietary calcium intake andabsorption , serum concentrations of calcium and phosphorus, and otherissues. There are no specific estrogen receptors in bone, and estrogenper se does not stimulate osteoblastic activity. However, estrogentherapy does reduce urinary calcium excretion, (it is presumed) byincreasing calcium absorption in the renal tubules.

Thus, while considerable evidence has accrued which ends credibility tothe existence of a causal relationship between estrogen deprivation andosteoporosis, the issue of whether estrogen deprivation is the primarycause of osteoporosis has not been resolved. Generally, in estrogendeficient premenopausal women, bone loss is accelerated but correspondsmore to the time of ovarian loss rather than to chronological age.Furthermore, women who are menstruating after age 50 have a slower rateof bone loss than do menopausal women of similar age.

5) Psychiatric Symptoms. The female climacteric may be quite stressful.Many menopausal women experience nervousness (easy excitability, mentaland physical unrest), irritability (uncontrollable crying, frequent rageor anger), anxiety (feelings of apprehension, uncertainty, fear and lossof self-image), and depression (inability to make decisions, apathy,psychomotor retardation, loss of libido or loss of emotional reaction).Most scientists feel that depression is not hormone-dependent. And thediagnosis of “involutional melancholia” which was previously used todescribe menopausal depression, has been deleted from the list ofacceptable diagnostic codes.

Additionally, the menopausal headache may have many causes which do notrelate to estrogen deprivation, such as the hormonal therapy itself.Estrogen therapy alters REM (“rapid eye movement”) sleep and the numberof waking episodes associated with hot flashes in menopausal women.

We have come to learn the affect that our composition has on theclimacteric only coincidentally after doing research related to therheumotoid-based diseases. The compositions seems to extend thepremenopause period, delaying menopause and therefore, postmenopause.The exact mechanism(s) responsible for this is unknown, although wesuspect that certain component(s) of the composition stimulate theadrenal glands, counteracting the decline in estrogen production andencouraging the production of yet another hormone, cortisone.

With respect to the affect that the compositions have onrheumatoid-based diseases, we do not know how the inflammationtriggering the onset of these diseases is controlled or abated, althoughthis is the affect the compositions have.

Acute inflammatory dermatoses and chronic inflammatory dermatoses areusually mediated by local or systemic immunological factors, althoughtheir causes generally remain a mystery. Thousands of specificinflammatory dermatoses exist. Some have both acute and chronic stages,others are most characteristic in early or late stages. In general,acute lesions last form days to weeks and are characterized byinflammation, edema and sometimes, epidermal, vascular or subcutaneousinjury. Chronic lesions, on the other hand, persist for months to yearsand often show significant components of altered epidermal growth(atrophy or hyperplasia) or dermal fibrosis.

Eczema falls into the category of acute inflammatory dermatoses. It isan umbrella clinical term embracing a number of pathogeneticallydifferent conditions. Al conditions are characterized by red,papoluvesicular, oozing and crusted lesions early on that withpersistence eventuate into raised, scaling plaques. It has an acutephase which can become a chronic eruption if untreated. With time,persistent lesions become less “wet” (fail to ooze or form vesicles) andbecome progressively scaly.

Urticaria or hives refers to a common disorder of the skin characterizedby localized mast cell degranulation and resultant dermal microvascularhypermeability falls into the category of acute inflammatory dermatoses.Individual lesions develop and fade usually within 24 hours, andepisodes may last for days or persist for months. Persistent urticariamay simply be the result of inability to eliminate the causative antigenor may herald underlying diseases. Lesions may vary from small pruriticpapules to large endematous plaques.

Erythema Multiforme falls into the category of acute inflammatorydermatoses. It appears to be a hypersensitivity response to certaininfections and drugs. Patients have array of lesions including macules,papules, vesicles and bullae, as well as the characteristic targetlesion consisting of a red macule or papule with a pale, vesicular oreroded center.

Psoriasis falls into the category of chronic inflammatory dermatoses. Itis sometimes associated with arthritis, myopathy, enteropathy,spondylitic heart disease and AIDS. Psoriatic arthritis may be mild orproduce deformities resembling the joint changes seen in rheumatoidarthritis. Most frequently affects elbows, knees, scalp, lumbosacralareas, and glans penis. Most typical lesion is well-demarcated, pink andsalmon-colored plaque covered by loosely adherent scales that arecharacteristically silver-white in color. Psoriasis can be the cause oftotal body erythema and scaling known as erythroderma.

Lichen Planus falls into the category of chronic inflammatorydermatoses. Pruritic, purple, polygonal papules are signs of this skindisorder. It is self-limiting and generally resolves spontaneously oneto two years after onset, often leaving zones of post-inflammatoryhyperpigmentation. Oral lesions may persist for years. Lesions areitchy, flat-topped papules that may coalesce locally to form plaquesoften highlighted by white dots or lines called Wickman's striae.Multiple lesions are characteristic and symmetrically distributed,particularly on the extremities, often about the wrists and elbows.

Gingivitis is the most common form of periodontal disease starting asinflammation of the marginal gingiva which is painless, although thegingiva may bleed on brushing. The disease spreads to involve theperiodontal ligament and alveolar bone. As the alveolar bone is slowlyresorbed, there is loss of periodontal ligament attachment between toothand bone. The soft tissue separates from the tooth surface, causing“pocket” formation with bleeding on probing and during chewing. Acuteinflammation may become superimposed on this chronic process, with theproduction of pus and formation of a periodontal abscess. Ultimately,extreme bone loss, tooth mobility, and recurrent abscess formation leadsto tooth exfoliation or may mandate tooth extraction. It is infectionassociated with the accumulation of bacterial plaque which may becomemineralized (“calculus”) and which can be prevented by appropriate oralhygiene measures including tooth brushing, flossing, antibacterial mouthrinses, and the removal of impacted food debris.

Immunity Disorders. The prior art has proposed methods and compositionsfor improving the immune response of humans using dietary supplementsfrom natural sources. Illustrative are U.S. Pat. Nos. 4,386,072;5,602,109; and 5,731,290 which disclose vegetable oils such as oils ofcotton seed, soybean, peanut, corn, sunflower seed, safflower, poppyseed, linseed and perilla for improving the immune response.

SUMMARY OF THE INVENTION

I. Topical Composition and Method of Treatment of Rheumatoid-BasedDiseases

a) For the treatment of rheumatoid-based diseases the composition of thepresent invention comprises:

300 to 1500 grams, and preferably 700 to 1000 grams of finely dividedpowder of safflower seeds (carthamust inctorius 1) admixed into 6 to 7gallons of warm water.

The method of treatment comprises:

bathing the patient in the composition for about 0.5 to 1.5 hours;

towel drying the patient;

allowing the residual composition to remain on the patient for 24 hours;and

repeating the treatment at least twice a week for 6 to 10 weeks orlonger.

(b) In another embodiment the composition of the present inventioncomprises:

150 to 1000 grams, and preferably 300 to 800 grams of an extract ofsafflower seeds admixed into 6 to 7 gallons of warm water.

The method of treatment comprises:

bathing the patient in the composition for about 0.5 to about 1.5 hrs;

towel drying the patient;

allowing the residual composition to remain on the patient for 24 hours;and

repeating the treatment at least twice a week for 6 to 10 weeks orlonger.

(c) Alternatively, the treatment of patients having rheumatoid-baseddiseases comprises massaging an extract of safflower seeds onto theaffected joint areas of the patient for about 5 to 20 minutes,preferably for 10 to 15 minutes.

II. Compositions and Method of Treatment for Menopause

For the treatment of menopause a combination of topical and oralformulations are used. The topical treatment is as above-described inI(a) and I(b), except that the duration of treatment is extended for aslong as necessary.

The oral component of the treatment comprises:

ingesting an oral formulation containing of from about 25 to 30 grams ofan extract of safflower, or 30 to 100 grams of finely divided safflowerseed twice a week as long as necessary.

While the compositions and treatments described in I and II abovedefines the specifics as best determined at present and supported bytesting on human patients, it is to be understood that a broader aspectof the invention encompasses treatment of rheumatoid-based diseases andmenopause by using a “therapeutically effective amount” of saidcompositions. “Therapeutically effective amount” refers to the amount ofan active agent sufficient to induce a desired biological result. Thatresult is the alleviation of the signs, symptoms, or causes of thediseases or conditions described under Reported Developments.

III. Method of Treatment of: Inflammatory Diseases, such as Eczema,Urticaria, Psoriasis, Erythema Multiforme and Lichen Planus,Inflammation of the Gums, and Chronic Localized Bodily Pain Derived FromAcute Injury

The treatment for the relief of inflammation and or pain associated withinflammatory dermatoses such as eczema, urticaria, psoriasis, erythemamultiforme and lichen planus, gingivitis, and acute injury in a mammalcomprises: topically administering to said mammal in need of suchtreatment a therapeutically effective amount of a finely divided powderof safflower seed having a particle size of 100 microns or less or itsextract sufficient to induce alleviation of signs, symptoms or causes ofinflammation or pain in a pharmaceutically acceptable carrier. The“Therapeutically effective amount” refers to the amount of an activeagent sufficient to induce a desired biological result. That result isthe alleviation of the signs, symptoms, or causes of the diseases orconditions described under Reported Developments. “Finely dividedpowder” denotes an average particle size of 100 microns or less.

IV. Method of Improving Immune Response

The method of treatment is preferably prophylactic, however, thetreatment can also be advantageously used where the immune system isweakened by disease such as prostate, lung, stomach, esophagus and bloodcancers. The method of prophylaxis and/or treatment comprising orallyadministering a prophylactically or therapeutically effective amount ofsafflower seeds or extract thereof sufficient to induce a desiredbiological result. The treatment comprises: ingesting an oralformulation containing of from about 25 to 30 grams of an extract ofsafflower seeds, or of from about 30 grams to about 100 grams of finelydivided safflower seeds at least two to three times a week.

The active ingredient is preferably combined with food products such asjelly, cheese, ice cream, chocolate and beverages.

Alternatively, the safflower seeds or extract thereof may beincorporated into typical pharmaceutical carriers for convenience.

Oral pharmaceutical dosage forms are either solid or liquid. The soliddosage forms are tablets, capsules, granules, and bulk powders. Types oforal tablets include compressed, chewable lozenges and tablets,sugar-coated or film-coated. Capsules may be hard or soft gelatincapsules, while granules and powders may be provided in non-effervescentor effervescent form with the combination of other ingredients known tothose skilled in the art.

Pharmaceutically acceptable carriers utilized in tablets are binders,lubricants, diluents, disintegrating agents, coloring agents, flavoringagents, and wetting agents. Sugar-coated tablets are compressed tabletsto which different layers of pharmaceutically acceptable substances havebeen applied. Film-coated tablets are compressed tablets which have beencoated with a water soluble polymers. Multiple compressed tablets arecompressed tablets made by more than one compression cycle utilizing thepharmaceutically acceptable substances previously mentioned. Coloringagents may also be used in the above dosage forms. Flavoring andsweetening agents are used in compressed tablets, sugar-coated, multiplecompressed and chewable tablets. Flavoring and sweetening agents areespecially useful in the formation of chewable tablets and lozenges.

Examples of binders include glucose solution, acacia mucilage, gelatinsolution, sucrose and starch paste. Lubricants include talc, starch,magnesium or calcium stearate, lycopodium and stearic acid. Diluentsinclude, for example, lactose, sucrose, starch, kaolin, salt, mannitoland dicalcium phosphate. Disintegrating agents include corn starch,potato starch, bentonite, methylcellulose, agar andcarboxymethylcellulose. Coloring agents include, for example, any of theapproved certified water soluble FD and C dyes, mixtures thereof, andwater insoluble FD and C dyes suspended on alumia hydrate. Sweeteningagents include sucrose, lactose, mannitol and artificial sweeteningagents such as sodium cyclamate and saccharin, and any number of spraydried flavors. Flavoring agents include natural flavors extracted fromplants such as fruits and synthetic blends of compounds which produce apleasant sensation. Wetting agents include propylene glycolmonostearate, sorbitan monooleate, diethylene glycol monolaurate andpolyoxyethylene laural ether. Film coatings includehydroxyethylcellulose, sodium carboxymethyl-cellulose, polyethyleneglycol 4000 and cellulose acetate phthalate.

Liquid oral dosage forms include aqueous solutions, emulsions,suspensions, solutions and/or suspensions reconstituted fromnon-effervescent granules and effervescent preparations reconstitutedfrom effervescent granules. Aqueous solutions include, for example,elixirs and syrups. Emulsions are either oil-in water or water-in-oil.

Elixirs are clear, sweetened, hydroalcoholic preparations.Pharmaceutically acceptable carriers used in elixirs include solvents.Syrups are concentrated aqueous solutions of a sugar, for example,sucrose, and may contain a preservative. An emulsion is a two-phasesystem in which one liquid is dispersed in the form of small globulesthroughout another liquid. Pharmaceutically acceptable carriers used inemulsions are non-aqueous liquids, emulsifying agents and preservatives.Suspensions use pharmaceutically acceptable suspending agents andpreservatives. Pharmaceutically acceptable substances used innon-effervescent granules, to be reconstituted into a liquid oral dosageform, include diluents, sweeteners and wetting agents. Pharmaceuticallyacceptable substance used in effervescent granules, to be reconstitutedinto a liquid oral dosage form, include organic acids and a source ofcarbon dioxide. Coloring and flavoring agents are used in all of theabove dosage forms.

Examples of preservatives include glycerin, methyl and propylparaben,benzoic acid, sodium benzoate and alcohol. Examples of non-aqueousliquids utilized in emulsions include mineral oil and cottonseed oil.Examples of emulsifying agents include gelatin, acacia, tragacanth,bentonite, and surfactants such as polyoxyethylene sorbitan monooleate.Suspending agents include sodium carboxymethylcellulose, pectin,tragacanth, Veegum and acacia. Diluents include lactose and sucrose.Sweetening agents include sucrose, syrups, glycerin and artificialsweetening agents such as sodium cyclamate and saccharin. Wetting agentsinclude propylene glycol monostearate, sorbitan monooleate, diethyleneglycol monolaurate and polyoxyethylene lauryl ether. Organic acidsinclude citric and tartaric acid. Sources of carbon dioxide includesodium bicarbonate and sodium carbonate. Coloring agents include any ofthe approved certified water soluble FD and C dyes, and mixturesthereof. Flavoring agents include natural flavors extracted from plantssuch fruits, and synthetic blends of compounds which produce a pleasanttaste sensation.

DETAILED DESCRIPTION OF THE INVENTION

Certain compositions of the present invention are oral while others aretopical, and accordingly, their method of administration are either oralor topical or a combination of oral and topical.

For oral compositions it is contemplated that any system which affordsingestion via the gastrointestinal tract can be used, such as powders,pellets, tablets, suspensions, gels, candy bars, chewing gums, syrupsand beverages.

For topical compositions it is contemplated that any system whichprovides delivery of the active ingredients to an appropriate site ofthe body can be used, such as dried and comminuted safflower seedscontained in a water-penetrable bag or container to be used in water,ointments, creams, lotions, solutions, dressings and patches,slow-release preparations and film-forming preparations. The topicalcompositions may contain certain pharmaceutical and therapeutical agentsthat can be included in the compositions either singularly or incombination. Such agents include: anti-inflammatory analgesics such assalicylic acid, salicylate esters and salts, acetylsalicylic acid,acetaminophen, phenylbutazone, indomethacin, fenoprofen, ibuprofen andketoprofen; local anesthetics such as benzocaine, lidocaine andbupivacaine; antibacterial agents such as sulfanilamide, sulfadiazine,sulfisoxazole and trimethoprim; antiseptic agents such as ethanol,isopropyl alcohol, chlorhexidine, hexachlorophene and benzoyl peroxide;anti-inflammatory corticosteroids such as progesterone, hydrocortisone,prednisone, triamcinolone and dexamethasone; and vasodilators such asniacin, nicotinate esters, diltiazem and indomethacin.

We have found that one of the most effective methodology of treatment isby bathing in water in which finely divided particles of raw safflowerseeds are dispersed. In this methodology the seeds of the safflower areremoved and comminuted to fine particle size, preferably 100 micron orless, packaged in a porous packet and immersed in warm bath water. Thepatient, while in the bath water then rubs the content aggressivelyuntil the content dissolves or at least homogeneously dispersed in thewater. The patient remains in the bath for 30 to 90 minutes whilesubjecting the inflamed rheumatoid area of the body to the therapeuticbath. We have found that for best results the ratio of ground safflowerseed to the volume of water is about 300 to 1500 grams of powder to 6 to7 gallons of water.

Alternatively, the safflower seeds may be dried to eliminate moisturethat might be present in raw safflower seeds, followed by comminution tothe desired particle size.

The porous packet is packaged in a moisture/gas impermeable package toprevent degradation of the content.

It is to be noted that the present invention utilizes seeds of saffloweror extract of safflower seeds and not the commercially available oil ofsafflower. While safflower oil has been found to be beneficial as acomponent of dietary supplements and as an important food source, itappears that certain trace amounts of ingredients are lacing in suchcommercially available oils without which the beneficial effect is notobtained as described by the present invention.

The extract of safflower seeds are obtained by methods known in the artfor extracting ingredients from naturally occurring sources andincludes:

the shelled safflower seeds are crushed and comminuted to a smallparticle size of 100 micron or less;

mixing the fine particle-size powder with an organic solvent, such asacetone, methylethylketone, diethylketone, methanol or ethanol;

allowing the mixture to stand at a low temperature, such as at roomtemperature, to dissolve soluble compounds from the powder;

separating the extract from the unsolvated material by filtration; and

evaporating or distilling the solvent to obtain the desired extract ofthe safflower powder.

Alternatively, the finely divided safflower powder can be mixed with hotmethanol or hot ethanol to accelerate the dissolution process.

Both the extract or the finely comminuted safflower powder can be madeinto pharmaceutical compositions as illustrated hereunder.

While it is possible to administer the finely divided safflower seed orits extract alone, and their topical administration via bathing ispreferred, it is practical to provide various forms of administrationfor the convenience of the patients. These forms include solid,semi-liquid, and liquid dosage forms, such as tablets, pills, powders,solutions and suspensions.

Topical Formulations

Topical formulations can be prepared by combining the finely dividedsafflower seed or its extract with conventional pharmaceutical carriersor diluents used in topical dry, liquid and cream formulations.Ointments and creams may be formulated with an aqueous or oil base withthe addition of suitable thickening or gelling agents.

Lotions may be formulated with an aqueous or oily base, and will includestabilizing agents, emulsifying agents, dispersing agents, suspendingagents, thickening agents, coloring agents and the like.

Powders may be formulated with the aid of any suitable powder base, suchas talc, lactose, starch and the like.

The ointments, pastes, creams and gels may contain excipients, such asparaffins, starch, tragacanth, cellulose derivatives, polyethyleneglycols, silicones, talc and zinc oxide.

The topical pharmaceutical formulations may include one or morepreservatives or bacteriostatic agents, such as methyl hydroxybenzoate,propyl hydroxybenzoate and benzalkonium chloride.

Another preferred form for topical delivery of the finely divided powderof safflower seed or its extract is a hot compress comprising:

a woven or non-woven fibrous wrap impregnated with said finely dividedsafflower seed or its extract, dried and packaged for use. Prior totreatment the impregnated fibrous wrap is immersed in warm water to atleast partially solubilize the active component and is wrapped aroundthe rheumatoid-based disease infected area.

Another preferred form of topical delivery is film-forming materialsloaded with the finely divided powder of safflower seed or its extract.Such film-forming materials are disclosed in U.S. Pat. No. 4,623,539 andis incorporated herein by reference.

The film-forming polymers include certain anionic, cationic and neutralpolymers.

A) Anionic polymers suitable as film-forming materials are representedby the generalized formula:

wherein

R is a polymeric chain or residue;

anionic ligands; and

M is a divalent cation of Mg⁺⁺, Ca⁺⁺, Zn⁺⁺ or Ba⁺⁺.

Specific anionic polymers include:

sulfated polysaccharides;

carboxylated polysaccharides;

cellulose derivatives; and

sulfated, sulfonated or carboxylated synthetic polymers.

Sulfated polysaccharides include sugars, cellulose, starch and glycogen.

Carboxylated polysaccharides include pectin, algin and karaya gum.

Cellulose derivatives include sodium ethylcellulose sulfate, sodiumcellulose acetate sulfate and sodium carboxymethyl cellulose.

B) Cationic polymers suitable for film-forming materials are representedby the following formulas:

wherein

R is a sugar residue;

R¹ is CH₃ or C₂H₅, and

M⁺⁺ is Mg⁺⁺, Ca⁺⁺, Zn⁺⁺ or Ba⁺⁺.

Examples of specific cationic polymers include chondrotoin sulfate,dermatan sulfate, keratosulfate, hyaluronic acid, heparin and chitin.

C) Neutral polymers suitable as film-forming materials include:

polysaccharides, such as fructans, mannans, galactomannans, glucomannas,dextran and starch amylose;

cellulose derivatives, such as methylcellulose, hydroxyethylcellulose,ethylhydroxyethyl cellulose and hydroxypropyl cellulose; and

synthetic polymers, such as polyvinylpyrrolidone, polyvinyl alcohol andthe ethylene oxide polymers.

These polymeric materials are capable of forming a film in the pHenvironment of 5.5 to 8.5 and contain atoms with polarizable electronsthereon such atoms being oxygen, nitrogen and sulfur. These atoms in thepolymeric materials in combination with the divalent cations of Ca⁺⁺,Mg⁺⁺, Zn⁺⁺ or Ba⁺⁺ provides for the formation of a film on a solidsurface, such as the skin of the patient. The ratio of the oxygen,nitrogen or sulfur atoms to the divalent cations of Ca⁺⁺, Mg⁺⁺, Zn⁺⁺ orBa⁺⁺ is preferably in the range of 7.7 to 1.

The film-forming materials described above are mixed with the finelydivided powder of safflower seed or its extract and suspended in anaqueous/alcoholic vehicle, such as ethanol, or incorporated into alotion or cream base. The ratio of the film-forming material to theactive ingredient is about 1 to 10 and preferably about 3 to 5.

Upon application, the formulation is deposited on the desired area andallowed to form a film which, by the presence of water in the skinenvironment, will allow slow delivery of the active agent onto the areabeing treated.

Oral Formulations

Formulations in the form of tablets, capsules, suspensions, solutionsand the like well-known in the pharmaceutical art are used for deliveryof the finely divided powder of safflower seed or its extract to thepatient.

Our compositions have been clinically tested on volunteers havingrheumatoid-based diseases suffering from minor to advanced arthriticand/or other rheumatoid-based symptoms and conditions. The resultsconfirm that the application of our compositions is a breakthrough inhealing patients afflicted with these diseases. It is expected that ourcompositions will replace many alternative pharmaceutical and surgicalremedies for the large majority of persons suffering from arthritis andrheumatoid-based diseases because (1) it cures the patient by reducingthe inflammation that triggers the onset of many rheumatic diseases,eliminating symptoms and preventing progressive damage to articularstructures; (2) it is non-toxic with no side effects; (3) treatment isnoninvasive and simple; and (4) if recurrence of certain diseasesymptoms does take place, usually one to two follow-up treatment(s)sufficiently achieves remission.

Clinical testing of our compositions have included laboratory testingdescribed hereunder.

Laboratory testing in RA is important and must be carefully coupled witthe clinical findings. In the effort to facilitate understanding of whycertain blood tests are performed, one must learn about the immunesystem, which in a nutshell is the body's natural defense againstforeign invaders such as bacteria or viruses. Many rheumatic diseasesare known as autoimmune diseases and can be traced to a defect in one'simmune system. The immune system fights its own body cells because itinterprets them as invaders. When an invader such as a virus enters thebody, the virus creates an antigen. The body's immune system fights theantigen by creating an antibody. When the immune system incorrectlydecides the body itself is an invader, it creates autoantibodies thatattack the body itself. The results of this process include inflammationof the joints, muscles, internal organs, skin, blood vessels, eyes ormucous membranes. Immunological blood tests, such as rheumatoid factor,antinuclear antibody, and Human Leukocyte Antigen tissue typing, areoften used to diagnose an autoimmune disease.

(1) Rheumatoid Factor

The hallmark of RA is the presence of rheumatoid factors (hereinafter,“RF”), which are anti-human immunoglobulins (hereinafter “IgMs”). Therheumatoid factor test measures whether a certain amount of abnormalantibody called RF is in the blood. “Classic” RF is an IgM antibodydirected against IgG and is detected in 80% of patients with RA.However, this test is not specific for RA and may be found at times inthe other connective-tissue diseases, in chronic inflammatory states,and occasionally in normal individuals. Its use as a screening test inall patients with arthritis should therefore be avoided. In the firstthree months of RA when the diagnosis is often difficult, RF is presentonly in one quarter of cases. By 1 year, almost all who will be RFpositive have become so. Why 20% of patients with RA do not develop IgMRF is not clear. Patients with positive RN, especially in high titer,tend to have more severe articular diseases, rheumatoid nodules, andsystemic manifestations.

(2) Antinuclear Antibody Tests.

Antinuclear antibody (hereinafter “ANA”) tests detect a group ofautoantibodies that are found in most people afflicted with lupus and ina few people with RA. The most important ANA is called anti-DNA, whichreacts with DNA (the chemical material in the nucleus of a cell thatmakes up the genetic component).

(3) Human Leukocyte Antigen Tissue Typing

These tests detect whether certain genetic markers or traits are presentin the blood. For example, B-27 is the name of a genetic marker that isalmost always present in people with ankylosing spodylitis (a diseaseinvolving inflammation of the sacroiliac joint and spine) and Reiter'ssyndrome (a disease involving inflammation of the urethra, eyes andjoints).

(4) X-Rays/Radiographs

Radiological findings in the joints in RA are related to the synovialmembrane inflammation. Early in the course of the disease roentgenogramsmay be normal. With time, the bones become demineralized withosteoporosis, especially in the regions adjacent to the joints(juxta-articular osteoporosis). In addition, the proliferative synovium,known as the pannus, can erode into the articular cartilage and bonecausing considerable damage. Increased synovial fluid production resultsin joint swelling that when coupled with the extension of theinflammation into the peri-articular tissues results in laxity of thesurrounding ligaments and adjacent tendons. Significant deformity ofjoints can develop, especially in the hands and feet as a result ofconcomitant mechanical stresses on the involved joints. Common clinicalfindings include swan neck, boutonniere, and ulnar deviationsdeformities of the hands and metatarsophalangeal subluxation of thefeet. Other joints, including the hips, knees, shoulders, elbows andankles, may have severe cartilage and bone changes. The upper cervicalspine may be involved with atlantoaxial subluxation, which may causespinal cord impingement by the odontoid process of the C2 vertebra.Intermittent radiographic evaluation of the neck may be warranted todetect slippage prior to this catastrophic occurrence.

(5) Joint Fluid Tests

Inserting a needle into a joint and removing or aspirating fluid form itcan provide the doctor with valuable information. Usually this procedureis conducted with local anesthetics. An examination of the fluid mayreveal what is causing the inflammation, such as uric acid crystals, asure sign of gout, or bacteria, a sign of infection. In addition, jointaspiration can sometimes relieve the pain of a badly swollen joint bydraining of some of the inflamed synovial fluid (the fluid thatsurrounds a joint, providing for smooth movement).

In testing a composition of the present invention it was unexpectedlydiscovered that the composition is also effective in healing certainsoft tissue rheumatic syndromes (hereinafter sometimes referred to a“STRS”), in addition to RA. These are syndromes that affect the tissuesand structures that surround a joint and produce pain, swelling orinflammation, including tendons, ligaments, bursae and muscles. Sincethese structures are near the joint, pain in these areas may easily bemistaken for arthritis, However, arthritis refers to inflammation in thejoint itself, not the structures around the joint.

One or more of the following factors can cause STRSs: overuse or injuryto the joint areas form repeated activity, incorrect posture or poorconditioning before exercise, an abnormal or poorly positioned joint orbone that stresses soft tissue structures, an infection, in associationwith other diseases or conditions like RA, often an unknown cause.

Pain is the major complain in people with an STRS. Pain usually startssuddenly. Since the structures involved are located near the joint,movements of that joint can be extremely painful and limited. Someconditions are associated with redness, warmth and swelling.

The two most common conditions favorably affected by our composition aretendinitis and carpal tunnel syndrome. Tendinitis is inflammation orirritation of the tendon, which is a thick cord that attaches muscle tobone. Tendons convey the power generated form muscles to move a bone.Carpal tunnel syndrome [hereinafter sometimes referred to as “CTS”] is acondition that causes pain, tingling, numbness and/or weakness in thefingers and thumb due to pressure on the median nerve. This nervecarries signals between the hand and brain. In the wrist, the mediannerve and several tendons that allow the fingers and thumb to bend passthrough the carpal tunnel (a tunnel created by the wrist bone and othertissue). When swelling or inflammation occurs around the tendons andnerve, pressure is increased within the carpal tunnel which affectsmedian nerve function, causing the symptoms of CTS.

With respect to STRSs, causes often include arthritis-related diseases,such as RA. Our composition has been highly effective in the treatmentof STRS patients with histories of RA, which comes as no surpriseconsidering the overwhelmingly positive clinical results of ourcomposition's application on RA patients.

A composition according to the present invention was tested on patientssuffering primarily form rheumatoid arthritis, as well asosteoarthritis, carpal tunnel syndrome and tendinitis. The method oftesting comprised:

The patient was placed in a private whirlpool spa where 700 grams of anextract of safflower powder was diluted in 6 to 7 gallons of warm water.The patient remained in the spa for 1.5 hrs after which the patient wastowel-dried and instructed not to shower for 24 hrs. In some instances,the extract was massaged onto the affected joint area for 15 minutes.

The following is a list of case studies representing patients treatedwith the composition.

Arthritis grading scale used is shown in Table VI.

TABLE VI Arthritis Grading Scale Grade Descriptive Evaluation 0 nodisease 1 documented disease that is asymptomatic 2 mild pain that isrelieved by nonopiate analgesics 3 severe pain that is not relieved byanalgesics 4 disabling pain that interferes with the activities of dailyliving

Table VII shows the Synopsis Chart.

TABLE VII Synopsis Chart Post- Duration Pre-Tx* Tx* Case Patient Age Sexof Disease Grade Grade Diagnosis  1 MK 84 F 35 Years 4 1 RA  2 PY 56 F26 years 4 1 RA/OA  3 TJ 65 F 12 years 3 1 RA  4 HK 44 F  4 years 4 1RA/CTS  5 SL 48 F 15 years 4 1 RA  6 AOP 58 F 29 years 4 2 CTS  7 JMC 70F 15 years 4 1 OA  8 FRB 65 M  6 years 4/3 1 RA  9 TK 75 F  3 years 3 1RA 10 MRM 89 F 13 years 4/3 2/1 CTS 11 WW 55 M 20 years 4 1 RA 12 AHP 70F  8 years 4 2 OA 13 MBG 85 F 16 years 4 1 RA 14 ACG 76 M 25 years 4 2RA/CTS 15 NS 67 F 20 years 4 2 RA/CTS 16 RP 67 M  7 years 3 n/a RA/CTS17 CJK 38 F  4 years 3 n/a RA/CTS 18 DGB 64 F  6 years 4 4 OA *Tx is anabbreviation for treatment

Clinical Summary Follows.

Case #1: MK is an 84 year old female (“F”) with a history of (“ho”) RAfor 35 years (“yrs”); previous medical history (“PMH”) is alsosignificant for congestive heart failure (“CHF”), myocardial infarction(“MI”) and diabetes; MK on multiple medications, i.e., coumadin,micronase, furosamide and lanoxin; pain increased (“++”) over the courseof 20 yrs to the point where it interfered with (“w/”) activities ofdaily living (“ADL”); Tx was undertaken for 3 months (“mths”) afterwhich mobility was regained. Now w/follow-up (“f/u”) of 2 yrs, MKremains asymptomatic.

Case #2: PY is a 56 year old F w/ h/o RA and OA for 26 yrs; PMH is alsosignificant for cerebrovascular accident (“CVA”), herniated nucleuspulposis in the lumbar region (“HNPL”), and erythmia; PY has takenNaproxen, other NSAIDS and steroidal drugs to no avail; pain ++ over thecourse of 18 yrs, to the point of interference w/ ADL; Tx was undertakenfor 2 mths w/ f/u Tx after 6 mths; f/u of 3 yrs reveals no recurrence ofinflammation or pain.

Case #3: TJ is a 65 F w/ h/o RA for 12 yrs; PMH is also significant forCVA; TJ has tried NSAIDS, DMARDS and Alkylating Agent s(“AAs”); pain ++for past 12 yrs, particularly when in between drugs; interference w/ADL, Tx undertaken for 1 mth; f/u reveals complete remission for past 1yr.

Case #4: HK is a 44 F w/ h/o RA and Carpal Tunnel Syndrome (“CTS”) for 4yrs; was recommended surgery to relieve pressure on median nerve; pain++ for 1 yr w/ interference w/ ADL; Tx undertaken for 3 weeks (“wks”);f/u reveals complete remission w/ no reports of stiffness, pressure ornumbness for past 3 yrs.

Case #5: SL is a 48 F F w/ h/o RA for 15 yrs systematically affectingmost of her joints; PMH is also significant for high blood pressure andCTS surgery; SL has tried methotrexate, auranofin, lederfen andcorticosteroids; pain ++ for 15 yrs w/ interference w/ADL; Tx undertakenfor 2 wks; f/u reveals her asymptomatic for past 5 mths.

Case #6: AOP is a 58 F w/ h/o RA CTS on both wrists for 29 yrs; PMHincludes CTS surgery for right median nerve, diabetes and high bloodpressure, AOP has tried NSAIDS; Tx is being currently administered with2 Txs undertaken w/in a 2 wk period; f/u reveals a decline in pain by50%.

Case #7: JMC is a 70 F w/ h/o OA in both knees for 15 yrs; PMH includesMI, four heart attacks, diabetes and obesity; JMC on Procardia,micronase, Lasix and Potassium; has tried NSAIDs w/++ of pain; 7 Txsundertaken for 2 mths; f/u asymptomatic for past 4 mths.

Case #8: FRB is a 65 year old male (“M”) w/ h/o RA affecting joints ofthe hand, knee, ankle, feet and neck for 6 yrs; PMH is also significantfor high blood pressure and anticoagulants; has tried various Txsincluding cortisone and NSAIDS; 6 Txs were undertaken for 5 wks; f/uasymptomatic for past 2 mths.

Case #9: TK is a 75 F w/ h/o RA for 3 yrs affecting her knees, hips,spine and shoulders; has tried NSAIDs, DMARDs and a combination ofCortisone w/ Relafin w/pain ++; 3 Txs undertaken for 2 wks; f/uasymptomatic for past 2.5 mths.

Case #10: MEM is a 89 F w/ h/o CTS affecting both wrists for 13 yrs; PMHincludes glaucoma, diabetes and a kidney operation; MEM has triedNSAIDS; 3 Txs being currently administered has reduced her pain by 60%.

Case #11: WW is a 55 M w/ h/o RA for 20 yrs affecting fingers of thehands,; has tried methotrexate, auranofin and corticosteroids; pain ++for 15 yrs; interference w/ ADL; Tx undertaken for 3 wks; f/uasymptomatic for past 9 mths.

Case #12: AHP is a 70 F w/ h/o OA for 8 years affecting both knees; PMHis also significant for high blood pressure and obesity; has triedNSAIDS after pain ++ over 3 years; 6 Txs undertaken during 5 wks whichhas diminished pain by 40% to date.

Case #13: MBG is a 85 F w/ h/o RA affecting knees and hips for 16 yrswith intense progression over the past 6 mths; PMH includes high bloodpressure, mitigated by Procardia; has tried NSAIDS but pain ++;currently 3 Tx administered that reduced pain by 50%.

Case #14: AGC is a 76 M w/ h/o RA affecting the neck, shoulders, elbows,wrists, hand joints, hips, knees and lower back; PMH is also significantfor MI and bypass surgery, CTS surgery, lyme disease and hernia;currently on anticoagulants, Quinidine, nitroglycerin, Procardia andNSAIDS for the RA but pain ++; 3 Txs have reduced the neck and shoulderpain by 20%.

Case #15: NS is a 67 F w/ h/o RA affecting the neck and shoulders for 20yrs and CTS affecting the wrists and fingers for 6 mths; PMH includescardiac arrhythmia, high blood pressure and bursitis; currently takingXantex, Digitalis, Lasix and Norwak; NSAIDS did not help the pain; 4 Txsreduces the pain by 70% over 5 wks.

Case #16: RP is a 67 M w/ h/o RA affecting knees and CTS progressivelyintensifying during past 7 yrs; currently taking NSAIDs; RP is under Tx,with some pain relief evident after one Tx.

Case #17: CJK is a 38 F w/ h/o CTS and pinched nerve, suspicion of RAdue to symptoms affecting jaw, shoulders, wrists, thumbs, and joints,knees, ankles, feet joints and upper back; currently under Tx, withprogress reported after one Tx.

Case #18: DGB is a 64 F w/ h/o OA of knees, severely debilitating herability to walk; also obesity; was taking NSAIDS; DGB is our onlypatient who did not improve after 5 Txs.

The composition arrests the development of the rheumatoid-baseddiseases, its nontoxic nature resolves any concerns about side effects.As such, it represents a breakthrough in healing patients afflicted withRA and RA-induced STRS', because it is the first non-toxic treatmentwith no side effects that reduces inflammation triggering the onset ofthese diseases.

Menopause patients were also treated by the methods and compositions ofthe present invention.

Twenty patients were treated between the ages of 42 and 58. Each patienthad experienced virtually all of the symptoms associated with menopause,such as hot flashes, headaches, weight gain, insomnia, decreased libido,depression, lethargy and joint pain. Each patient was “in menopause”,having had her last period between 7 months and 4 years prior to thetreatment. Ten patients were treated only topically using the methoddescribed in connection with treating patients with rheumatoid-baseddiseases. The other ten patients were treated, in addition to thetopical treatment, with an oral formulation. The oral formulation, a“tea” containing 25 to 30 grams of the finely divided powder ofsafflower seed, was consumed twice a week for four weeks.

The result, based on evaluation of input from each patient, was:

patients who were treated topically exclusively, experienced normalmenstrual period within 4 weeks after the treatment; while patientstreated both topically and orally experienced menstruation within thetreatment period itself. This result was in contrast to a group ofpatients not treated whose frequency of menstruation was random andirregular.

A composition of the present invention was tested for effectiveness inrelieving of inflammation and/or pain associated with inflammatorydermatoses such as eczema, urticaria, psoriasis, erythema multiforme,and lichen planus; inflammation of the gums (also known as gingivitis);and pain associated with acute injury/accident. This was aone-application, randomized study conducted in 145 patients: 75 of whomwere afflicted with various inflammatory dermatoses most notablyconsisting of eczema or psoriasis, 35 of whom had gingivitis and 35 ofwhom had chronic pain from impact derived from an injury.

With respect to subjects afflicted with inflammatory dermatoses andgingivitis, pain and inflammation were assessed in the morning uponsubject's awakening (baseline), and 24 hours after application.Analgesic response was determined using the sum of pain intensitydfferences (SPID), and medical examinations to evaluate inflammationbased on degree of swelling and discoloration (redness) The compositionwas significantly superior to the placebo in improving SPID, andrelieving inflammation. With respect to subjects afflicted with chronicpain derived from sudden impact, pain, stiffness and/or inflammationwere also assessed in the morning upon subject's awakening, and 24hours, 48 hours and 72 hours after application. Analgesic response wasdetermined using the sum of pain intensity differences (SPID), the sumof stiffness intensity differences (SSID), and when appropriate, medicalexaminations. Once again, the composition was significantly superior tothe placebo in improving SPID, SSID and relieving inflammation.

The details of the testing were as follows.

Of the 75 subjects, only subjects already diagnosed with inflammatorydermatoses such as eczema, urticaria, psoriasis, erythema multiforme,and lichen planus on their arms, volar and forearm areas and morningpain were accepted. 40 of these subjects had eczema, 30 had psoriasisand the remaining 5 had either urticaria, erythema multiforme or lichenplanus. These subjects consistently experienced characteristicdermatosis and pain and were likely to be better able to detect,quantify and measure changes in their pain. Of the 35 subjects withgingivitis, only those subjects with dental records diagnosing them withperiodontal disease were accepted. Of the 35 subjects who had chronicpain from impact derived from an injury, only those subjects who hadexperienced pain for at least 2 years in the same localized areagenerated from sudden impact such as an accident or injury wereaccepted. These subjects were required to suffer from morning pain andstiffness. Inflammation of the area often accompanied these symptoms.

All subject considered for enrollment stated on their screening formsthat they were told by their personal physicians that they had therelevant affliction. Subjects were enrolled in the study only if thestudy's examining physician also determined upon physical examinationthat they had the relevant disorder. 67 subjects were rejected by thestudy physician at screening for not meeting the criteria's for thedisorders. Approximately 48% of all subject were receiving activetreatment for their conditions. To participate in this study, subjectshad to be willing to discontinue use of medications for analgesia orinflammation for at least 7 days before applying the treatment. Onlysubjects who could make the required clinic visits, who the investigatorbelieved were mentally competent to carry out the study procedure, andwhose symptoms of severity was appropriate for treatment were enrolledin the study.

Before the study was begun, a medical history was obtained and aphysical examination conducted on all subjects. Treatment was dispensedto the subjects as follows:

(A) With respect to those 75 subject afflicted with various inflammatorydermatoses (most notably consisting of eczema or psoriasis), subjectswere instructed to rate the pain and inflammation in their armsimmediately upon awakening. Then they were to apply the treatment byplacing their arms in an aqueous solution consisting of 0.5 lb ofgrounded product and distilled water for a period of 45 minutes. Afterthe treatment, subjects were to rate the pain and inflammation on ascale of 1 to 5 24 hours later. They were to refrain from washing thetreated area during this time. Subjects were told specifically not toproceed with the study procedure unless they had at least moderatebaseline pain (a 3 on the scale of 1 to 5). The requirement of at leastmoderate pain was deemed necessary for subjects to be able to detect andmeasure a change in pain level. The primary effectiveness variables asstated in the protocol were relief of pain and inflammation in the arm.

(B) Similarly, with respect to those 35 subjects with chronic pain fromimpact derived from an injury, subjects were instructed to rate the painand inflammation in the afflicted area immediately upon awakening. Thenthey were to apply the localized are with an aqueous solution consistingof 0.5 lb of grounded product and distilled water for a period of 45minutes. After the treatment, subjects were to rate the pain, stiffnessand inflammation on a scale of 1 to 5 24 hours later, after which asecond treatment was immediately applied and subjects rated the pain,stiffness and inflammation on the same scale and second time 48 hoursafter the initial rating. A final treatment was then immediately applied72 hours after in the initial rating and a final rating of pain,stiffness and/or inflammation was assessed after this last (third)application. Subjects were to refrain from washing the treated area inthe interim period between each individual rating and treatment.Subjects were told specifically not to proceed with the study proceduresunless they had at lest moderate baseline pain (a 3 on a scale of 1 to5). The requirement of at least moderate pain was deemed necessary forsubjects to be able to detect a measure of change in pain level. Theprimary effectiveness variables as stated in the protocol were relief ofpain or sensation of restricted motion and inflammation in the localizedarea.

(C) With respect to those 35 subjects with gingivitis, pain andinflammation were assessed in the morning upon subject's awakening(baseline), and 24 hours later (12 hours after application). Subjectswere to apply 1 oz of product in 1 oz of distilled water by massagingthe gum area for exactly 4 minutes that evening before sleeping. Theywere to refrain from rinsing after application. After the treatment,subjects were to rate the pain and inflammation on a scale of 1 to 5 12hours later. Once again, subjects were told specifically not to proceedwith the study procedure unless they had at least moderate baseline pain(a 3 on a scale of 1 to 5). The requirement of at least moderate painwas deemed necessary for subjects to be able to detect and measurechange in pain level. The primary effectiveness variables as stated inthe protocol were relief of pain and inflammation in the gums. Withrespect to each of the three treatment groups, a final medicalexamination was conducted by the study physician on each subjectindividually approximately 24 hours after the last treatment wasapplied.

All 145 subjects completed the study. The demographic and backgroundcharacteristics of the subject population were unremarkable. There wereno clinically important differences between or within treatment groups.Pain relief (a decrease in pain intensity) and inflammation relief (adecrease in inflammation severity) were the primary effectivenessvariables. On the basis of SPID derived from the pain scores, SSIDderived from the sensation of stiffness scores, and the final medicalexamination conducted on each subject by the study physician, thecomposition significantly reduced pain intensity and inflammationseverity.

Of the 175 subjects with inflammation dermatoses, 23 had rated theirpain at a level of 3, 33 at a level of 4, and 19 at a level of 5. About69% of these subjects rated their pain at a level of 1 or 2, with all 23subjects with an initial pain self-rating level of 3, resulting in arating of 1 post treatment. Similarly, inflammation degrees declinedsignificantly at least 2 points in every case. Most very severe (5) andsevere (4) cases became mild (2) or moderate (3). 30% of subjectsreporting a 3 or above rated their inflammation “none” (1) posttreatment. The study physician confirmed the subjects' ratings withrespect to inflammation using standard scales of redness and swelling.

With respect to those 35 patients with chronic pain from impact derivedfrom an injury, 31 subjects had rated their pain at level 5, and 4 hadrated their pain at a level 4. Out of the 31 subjects who had ratedtheir pain as very severe, 21 rated their pain after the threetreatments at 2 or moderate, and the remaining 10 rated their pain at 1or none. The 4 subjects with an initial level 4 pain rating experienceda level 2 rating each after the three treatments. 26 subjects ratedtheir stiffness at a level 4. Among these, 24 rated stiffness at 1 posttreatment, 1 rated stiffness at 2 post treatment, and 1 rated stiffnessat 3 post treatment. 9 subjects had initially rated their stiffness atlevel 5. Among these, 3 subjects rated their stiffness at 3 posttreatment, 4 rated their stiffness at 2 post treatment, and 2 ratedtheir stiffness at 1 post treatment. Similarly, in 34.3% of casesreporting inflammation, 20% experienced a reduction by 1 level, and theremainder reported a reduction of inflammation by 2 levels.

Of the 35 subjects suffering from gingivitis, 30 initially rated theirpain at 4, and 5 initially rated their pain at 3. 33 subjects ratedtheir pain post treatment at 2 including the 5 with an initial painrating of 3, and the remaining 3 subjects rated their pain at 1 posttreatment. The study physician noted a one level decrease ininflammation rating in about 57% of these cases, and a two leveldecrease in inflammation rating in the remaining subjects.

A long-term study was conducted on volunteers to generate informationwhether a diet containing safflower seeds would have an effect on theimmune system for lowering the incidence of certain cancer.

In the treatment, a dietary supplement was used in the form of cheesethat is easily prepared and stored under refrigeration. Thesafflower-containing cheese was prepared as follows.

One gallon of pasteurized bovine milk was heated to 75° F. in acontainer, and 3 grams of powdered safflower seed was mixed with theheated milk. The mixture was stirred for 5 minutes to obtain a completedilution after which the mixture was put aside for about four hours tocoagulate. At coagulation a jelly-like textured component is obtainedwhich settled on the bottom of the container and a yellow watery liquidrose to the top of the container. The yellow water liquid was discardedand the jelly-like textured component was poured into a cheesecloth bagand securely closed. After about four hours the textured componentmetamorphasized within the cheesecloth bag into cheese and wasrefrigerated.

A placebo cheese was prepared using the same method of preparation asabove-described without the safflower seed.

The study was conducted as follows.

During a screening process by physicians, 250 men and women wereselected in a rural community. Families with incidence of cancer wereenrolled. From within a family those related by blood but not bymarriage were selected. From within the selected group only those wereaccepted who had a blood relative with a diagnosed cancer such as cancerof the prostate, lung, stomach, esophagus and blood. For example, afamily where a father and one of his sons or daughters were diagnosedwith cancer, only those were included in the study who, at the time ofthe screening, had diagnosed to be free of cancer. The rationale for theselection was that individuals free of cancer who had a close relativehaving cancer had a greater tendency of developing a cancer and passingthe genes of the disease on to their children and grandchildren.

The participants were examined and were of good general health andbetween the ages of 45 and 60. All participants met the followingadditional required criteria: (a) a daily diet including five servingsof fruits and vegetables, and approximately 25-30 grams of whole grainbreads or cereals; (b) a diet of limited saturated fat; (c) weightcontrol (none of the 250 participants were obese); (d) regular exerciseof at least 30 minutes a day; (e) no tobacco intake; and (f) limitedconsumption of alcohol.

The participants were divided into two groups with approximately equalnumbers in each group: a placebo group and a non-placebo group. Theprescribed treatment consisted of consumption of two ounces of placebocheese three times a week by each individual in the placebo group, andconsumption of two ounces of the non-placebo cheese three times a weekby each individual in the non-placebo group.

The participants were monitored and checked by physicians twice a yearfor more than 10 years. Those individuals who at the time of anexamination showed any sign of cancer were advised to see their ownphysician to obtain traditional treatment.

The study is ongoing. As of now, the following result appears to beencouraging: those assigned to the non-placebo group had about 84% fewerprostate, lung, stomach, esophagus or blood cancer develop as comparedto those in the placebo group.

This invention has been described in detail with particular reference tocertain preferred embodiments thereof, but it will be understood thatvariations and modifications can be effected within the spirit and scopeof the invention.

What is claimed is:
 1. A method for the prevention or minimization ofthe effect of catabolic illness by enhancing the immune response of apatient consisting of: orally administering to said patient in need ofsuch prevention or minimization of the effect of catabolic illness atherapeutically effective amount of a composition sufficient to inducealleviation of signs, symptoms or causes of catabolic illness consistingof about ten parts of a finely divided powder of safflower seeds havinga particle size of 100 microns or less; or an extract of safflowerseeds; and one part of a pharmaceutically acceptable carrier.
 2. Themethod of claim 1 wherein said composition is administered to saidpatient at least three times a week.
 3. The method of claim 1 whereinsaid pharmaceutically acceptable carrier is selected from the groupconsisting of jelly, cheese, ice cream, chocolate and beverages.
 4. Themethod of claim 1 wherein said pharmaceutically acceptable carrier is asolid selected from the group consisting of tablets, capsules, granules,bulk powder and lozenges.
 5. The method of claim 1 wherein saidpharmaceutically acceptable carrier is a liquid selected from the groupconsisting of solutions, emulsions, suspensions, elixirs and syrups. 6.A method for the minimization of the effect of catabolic illness byenhancing the immune response of a patient who is at a high risk ofdeveloping cancer consisting of orally administering to said patient inneed of such treatment a therapeutically effective amount of acomposition sufficient to induce alleviation of signs, symptoms orcauses of catabolic illness consisting of about ten parts of a finelydivided powder of safflower seeds having a particle size of 100 micronsor less and one part of a pharmaceutically acceptable carrier.
 7. Themethod of claim 6 wherein said composition is administered to saidpatient at least three times a week.
 8. The method of claim 6 whereinsaid pharmaceutically acceptable carrier is selected from the groupconsisting of jelly, cheese, ice cream, chocolate and beverages.
 9. Themethod of claim 6 wherein said pharmaceutically acceptable carrier is asolid selected from the group consisting of tablets, capsules, granules,bulk powder and lozenges.
 10. The method of claim 6 wherein saidpharmaceutically acceptable carrier is a liquid selected from the groupconsisting of solutions, emulsions, suspensions, elixirs and syrups. 11.A method for the minimization of the effect of catabolic illness byenhancing the immune response of a patient who is at a high risk ofdeveloping cancer consisting of: orally administering to said patient inneed of such treatment a therapeutically effective amount of acomposition sufficient to induce alleviation of signs, symptoms orcauses of catabolic illness consisting of about ten parts of an extractof safflower seeds and one part of a pharmaceutically acceptablecarrier.
 12. The method of claim 11 wherein said pharmaceuticallyacceptable carrier is selected from the group consisting of jelly,cheese, ice cream, chocolate and beverages.
 13. The method of claim 11wherein said pharmaceutically acceptable carrier is a solid selectedfrom the group consisting of tablets, capsules, granules, bulk powderand lozenges.
 14. The method of claim 11 wherein said pharmaceuticallyacceptable carrier is a liquid selected from the group consisting ofsolutions, emulsions, suspensions, elixirs and syrups.